The prion protein as a receptor for amyloid-β

Abstract

Increased levels of brain amyloid-beta, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer's disease. Increased amyloid-beta can cause synaptic depression, reduce the number of spine protrusions (that is, sites of synaptic contacts) and block long-term synaptic potentiation (LTP), a form of synaptic plasticity; however, the receptor through which amyloid-beta produces these synaptic perturbations has remained elusive. Laurén et al. suggested that binding between oligomeric amyloid-beta (a form of amyloid-beta thought to be most active) and the cellular prion protein (PrP(C)) is necessary for synaptic perturbations. Here we show that PrP(C) is not required for amyloid-beta-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-beta-mediated synaptic defects do not require PrP(c).

CSF prion protein concentration and cognition in patients with Alzheimer disease

“…2 Even more recently, evidence of PrP C acting as an Aβ oligomer receptor has emerged. [3][4][5][6] Yet, the potential impact on physiologic processes associated with learning and memory such as long-term potentiation and synaptic plasticity have been discussed rather controversially. By acting as an Aβ oligomer receptor, initiation of cascades leading to neuronal on which selective interactions with many ligands and transmembrane signaling pathways translate into wide-range consequences upon both physiology and behavior."…”

“…2 Especially PrP C 's role as a potential Aβ oligomer receptor and their conjoint impact on long-term potentiation (LTP), synaptic plasticity and neuronal death have been discussed controversially. [3][4][5][6] Although the overall expression of PrP C in the brain appears to be similar in healthy Background/Objective: PrP c has been suggested to play a role in aD pathophysiology. csF concentrations of PrP c have been shown to be reduced in aD compared with healthy controls.…”

The P’s and Q’s of cellular PrP-Aβ interactions

“…Such assumptions do not apply to wild-type mice, which may comprise a PrP expression. 49,50 More recently, however, Freier et al reported that standardized Aβ-derived diffusible ligand (ADDL) preparations disrupt hippocampal synaptic plasticity in a PrP-dependent manner and that Aβ obtained from ex vivo human material does the same. Furthermore, using monoclonal antibodies directed at two different PrP C epitopes, these and other authors successfully blocked the Aβ-mediated disruption of synaptic plasticity.…”

Alzheimer’s Amyloid-β Oligomers Rescue Cellular Prion Protein Induced Tau Reduction via the Fyn Pathway

“…14 In contrast, some studies indicate that PrP C is not required for Aβ oligomer-induced cognitive impairment since the PrP C expressing and knockout mice have no difference in Aβ oligomer-induced synaptic depression, spine density loss, and deficiency of long-term potentiation. 15 Two intracerebroventricular injections of Aβ oligomers to wild-type or PrP C null mice have suggested no PrP C effect on Aβ oligomer-induced memory dysfunction, 10 and modulation of PrP C in AD transgenic mouse models shows no effect on the impairment of the hippocampal synaptic plasticity. 16 Furthermore, PrP C deficiency does not ameliorate abnormal neural network activity or cognitive dysfunction in one type of AD model mice.…”